Reassessment of reimbursement status for lipid-lowering medicines,
ATC Group C10
March, 16 2007
Introduction
By the end of 20041, the Danish Parliament decided that decisions on
general reimbursement for medicinal products should be subject to periodic
reassessment.
The reassessment aims at assessing whether the assumptions underlying the
original decision on granting or not granting general, including restricted,
reimbursement, are still valid.
The Danish Medicines Agency is currently reassessing the reimbursement
status of all medicinal products over a period of five years, and the below
decisions will conclude the reassessment of the reimbursement status of
lipid-lowering medicines (ATC Group C10).
The decisions and accompanying justifications are directed towards
companies with medicinal products in the indicated ATC groups with
marketing authorisations in Denmark on 15 March 2007.
We enclose an appendix with a list of the medicinal products from your
company which the decision concerns.
The decisions entail an overall relaxation of the reimbursement status of
lipid-lowering medicines and will support treatment with lipid-lowering
medicines when the patient suffers from hyperlipidemia requiring
medication therapy and will encourage the use of the cheaper statins which
are eligible for general reimbursement, where possible, alone or in
combination with one of the other lipid-lowering substances.
1
In connection with the adoption of Act no. 1431 of 22 December 2004 on
Amendment of the Act on National Health Insurance. The amendment entered into
force on 1 January 2005. The Act on National Health Insurance was replaced by the
Danish Health Care Act; Act no. 546 of 24 June 2005. The reassessment rules remain
unchanged under the Health Care Act.
Journal no:
5315-8
Our ref: Lipid Reassessment.
Decision.b.160307
This decision is presented as a collective decision on the reimbursement
status of all lipid-lowering medicines (ATC Group C10). It should be
emphasised, however, that the Danish Medicines Agency has carried out a
specific assessment of all medicines covered by the reassessment, including
all products included in the attached list of your company’s medicinal
products.
As an introduction, the decisions made, with accompanying justifications,
are outlined below, followed by general remarks on consumption and
consumption developments, quotes from the legal basis, presentation of the
case and complaints guidance.
1. General reimbursement
(simvastatin, lovastatin and pravastatin)
Decision
Effective from 23 April 2007, the Danish Medicines Agency grants general
reimbursement without restriction for all medicinal products with
marketing authorisations in Denmark on 15 March 2007 that contain one of
the following statins (C10AA):
•
•
•
C10AA01: Simvastatin
C10AA02: Lovastatin
C10AA03: Pravastatin
Justification
This decision was based on Section 144 (1) of the Danish Health Care Act,
cf. Section 1 (1) and (2) of the Executive Order on Reimbursement2.
For the sake of good order, it is emphasised that the decision is not
directed towards medicinal products containing the statins
mentioned above, which are not classified in ATC group C10AA,
e.g. combination products, cf. below.
In reaching the decision, we have emphasised the fact that medicinal
products containing the statins simvastatin, lovastatin and pravastatin are
all useful first choices in the treatment of most hyperlipidemia cases.
In our clinical evaluation of the medicinal products, we have given
emphasis to the Danish Society of Cardiology’s clinical guidelines for the
prevention of cardiovascular diseases3, the recommendations and
2
Executive Order no. 180 of 17 March 2005 on reimbursement of medicinal products.
The interdisciplinary task group for prevention of cardiovascular disease in Denmark
established by the Danish Society of Cardiology. Clinical guidelines on the prevention
of cardiovascular disease in Denmark (“Kliniske retningslinier for forebyggelse af
3
2
background notes on lipid-lowering medicines by the Institute for Rational
Pharmacotherapy4, and NICE’s technological evaluation of statins5
supplemented by the SPARCL study6 published subsequently.
This is described in more detail in the Reimbursement Committee’s
recommendation of 7 September 2006, to which we refer.
Furthermore, we have attached importance to the fact that the average
lowest daily treatment price in the period 22 May 2006 – 31 July 2006 was
between DKK 0.91 and DKK 3.26 for these medicinal products.
The Reimbursement Committee’s recommendation of 7 September 2006
includes an account of the prices and doses on which the Reimbursement
Committee’s recommendation for the reimbursement status of the
medicines was based. We refer to the information stated by the
Reimbursement Committee. The prices and price level developments since
then do not justify a change of the assessment.
On this background, the Danish Medicines Agency assesses that the
reimbursement prices of these medicines are reasonable compared to the
therapeutic value of the products.
Reference is further made to the details indicated below on the
consumption and consumption development as well as our comments to the
consultation responses received.
2. Restricted reimbursement
(fluvastatin, atorvastatin, rosuvastatin, cholestyramine, colestipol,
acipimox, ezetimibe and combination of simvastatin and ezetimibe)
Decision
kardiovaskulær sygdom i Danmark”). Danish Society of Cardiology, 2004
(www.cardio.dk).
4
Institute for Rational Pharmacotherapy. Lipid-lowering medicinal products –
Recommendations and background notes (“Lipidsænkende lægemidler Rekommandationer og baggrundsnotater”). Institute for Rational Pharmacotherapy,
2005 (www.irf.dk).
5
National Institute for Health and Clinical Excellence (NICE). Statins for the
prevention of cardiovascular events. Technology Appraisal 94. NICE, 2006
(www.nice.org).
6
SPARCL investigators. High-dose atorvastatin after stroke or transient ischemic
attack. N Eng J Med 2006; 355: 549-59.
3
Effective from 23 April 2007, the Danish Medicines Agency grants
restricted reimbursement for all medicinal products with marketing
authorisations in Denmark on 15 March 2007 that contain one of the
following substances:
•
•
•
•
•
•
•
•
C10AA04: Fluvastatin
C10AA05: Atorvastatin
C10AA07: Rosuvastatin
C10AC01: Cholestyramine
C10AC02: Colestipol
C10AD06: Acipimox
C10AX09: Ezetimibe
C10BA02: Combination of simvastatin and ezetimibe
General reimbursement for these medicinal products is restricted for:
“Patients with hyperlipidemia necessitating treatment for whom
therapy with statins eligible for general reimbursement without
restriction has proved insufficient or who do not tolerate these
medicines.”
Justification
This decision was based on Section 144 (1) of the Danish Health Care Act,
cf. Section 1 (1), (2) and (4) of the Executive Order on Reimbursement.
Reimbursement for medicinal products subject to restricted reimbursement
is conditional on the doctor endorsing the prescription with
“reimbursement” (“tilskud”), cf. Section 1 (4) of the Executive Order on
Reimbursement.
The Danish Medicines Agency assesses that the effect of the statins is
largely a class effect, and the decision to grant restricted reimbursement for
fluvastatin, atorvastatin and rosuvastatin is therefore justified by the
reimbursement prices of the medicinal products, cf. below.
The Danish Medicines Agency assesses that medicinal products containing
the anion exchangers colestipol and cholestyramine and the nicotinic acid
derivative acipimox each have their place in the therapy, mainly as a
supplement to statins.
We have attached importance to the consumption data for the more recent
ezetimibe which indicates that the substance is primarily used as a
supplement to statins and not as first-choice therapy for hyperlipidemia
necessitating treatment. However, the Danish Medicines Agency will
carefully follow developments in the consumption of this substance.
4
As far as the combination of simvastatin and ezetimibe is concerned, it is
assessed that in the cases where both substances are needed, the
combination may result in better compliance than if the substances are
administered individually. However, treatment with a cheaper statin alone
is the first-line regimen for patients with hyperlipidemia necessitating
treatment, and we will therefore follow the consumption developments
carefully.
In our clinical evaluation of the medicinal products, we have given
emphasis to the Danish Society of Cardiology’s clinical guidelines for the
prevention of cardiovascular diseases7, the recommendations and
background notes on lipid-lowering medicines by the Institute for Rational
Pharmacotherapy8, and NICE’s technological evaluation of statins9
supplemented by the SPARCL study10 published subsequently.
This is described in more detail in the Reimbursement Committee’s
recommendation of 7 September 2006, to which we refer.
We have attached importance to the fact that the average lowest daily
treatment price in the period 22 May 2006 – 31 July 2006 was between
DKK 8.50 and DKK 24.32 for these medicines.
By way of comparison, the average lowest treatment price for simvastatin,
lovastatin and pravastatin was between DKK 0.91 and DKK 3.26.
The Reimbursement Committee’s recommendation of 7 September 2006
includes an account of the prices and doses on which the Reimbursement
Committee’s recommendation for the reimbursement status of the
medicines was based. The Danish Medicines Agency refers to the
information stated by the Reimbursement Committee. The prices and price
level developments since then do not justify a change of the assessment.
It is our assessment that for the large group of patients who can receive
treatment solely with, or based on, one of the statins for which general
7
The interdisciplinary task group for prevention of cardiovascular disease in Denmark
established by the Danish Society of Cardiology. Clinical guidelines on the prevention
of cardiovascular disease in Denmark (“Kliniske retningslinier for forebyggelse af
kardiovaskulær sygdom i Danmark”). Danish Society of Cardiology, 2004
(www.cardio.dk).
8
Institute for Rational Pharmacotherapy. Lipid-lowering medicinal products –
Recommendations and background notes (“Lipidsænkende lægemidler Rekommandationer og baggrundsnotater”). Institute for Rational Pharmacotherapy,
2005 (www.irf.dk).
9
National Institute for Health and Clinical Excellence (NICE). Statins for the
prevention of cardiovascular events. Technology Appraisal 94. NICE, 2006
(www.nice.org).
10
SPARCL investigators. High-dose atorvastatin after stroke or transient ischemic
attack. N Eng J Med 2006; 355: 549-59.
5
reimbursement without restriction has been granted, the reimbursement
prices of the medicinal products listed above are not reasonable compared
to the therapeutic value.
For patients with hyperlipidemia necessitating treatment, in whom therapy
with the statins eligible for general reimbursement without restriction has
proved insufficient, or who do not tolerate these medicines, it is our
assessment that the reimbursement prices of the mentioned medicinal
products are reasonable compared to their therapeutic value.
Reference is further made to the below information on the consumption
and consumption development as well as our comments to the consultation
responses received.
3. Restricted reimbursement
(fibrate)
Decision
Effective from 23 April 2007, the Danish Medicines Agency grants
restricted reimbursement for all medicinal products with marketing
authorisations in Denmark on 15 March 2007 that contain the fibrate:
•
C10AB04: Gemfibrozil
General reimbursement for these medicinal products is restricted for:
“Patients with isolated, severely elevated triglycerides or patients
with combined hyperlipidemia, possibly combined with statin.”
Justification
The decision was based on Section 144 (1) of the Danish Health Care Act,
cf. Section 1 (1), (2) and (4) of the Executive Order on Reimbursement.
Reimbursement for medicinal products subject to restricted reimbursement
is conditional on the doctor endorsing the prescription with
“reimbursement” (“tilskud”), cf. Section 1 (4) of the Executive Order on
Reimbursement.
We have emphasised the fact that medicinal products containing the statins
simvastatin, lovastatin and pravastatin should be used as first choice
treatment of most cases of hyperlipidemia, cf. above, but that gemfibrozil
should be used as first choice for isolated, severely elevated triglycerides
and in case of combined hyperlipidemia.
In our clinical evaluation, we have given emphasis to the Danish Society of
Cardiology’s clinical guidelines for the prevention of cardiovascular
6
disease11, and the recommendations and background notes on lipidlowering medicines by the Institute for Rational Pharmacotherapy12.
This is described in more detail in the Reimbursement Committee’s
recommendation of 7 September 2006, to which we refer.
Furthermore, we have attached importance to the fact that the average
lowest daily treatment price in the period 22 May 2006 – 31 July 2006 was
DKK 9.22 for this medicinal product. The prices and price level
developments since then do not justify a change of the assessment.
It is our assessment that for the large group of patients who can receive
treatment solely with, or based on, one of the statins for which general
reimbursement without restriction has been granted, the reimbursement
prices of medicinal products containing the fibrate gemfibrozil are not
reasonable compared to the therapeutic value.
However, we believe that the reimbursement prices of the medicinal
products containing the fibrate gemfibrozil are reasonable compared to the
therapeutic value when treating patients with isolated severely increased
triglycerides or patients with combined hyperlipidemia, possibly in
combination with statin.
Reference is further made to the below information on the consumption
and consumption development as well as our comments to the consultation
responses received.
Consumption data for lipid-lowering medicines
The decision by the Danish Medicines Agency on the reimbursement status
for the lipid-lowering medicines relies on information about consumption
and turnover of lipid-lowering medicines and the number of people
receiving treatment with these medicines in the years 2001-2005.
Preliminary consumption figures and the developments in consumption in
2006 do not justify a change of the evaluation.
In 2005, 307,000 individuals received treatment with medicinal products
from ATC group C10 – of whom 303,400, corresponding to 99 percent,
11
The interdisciplinary task group for prevention of cardiovascular disease in
Denmark established by the Danish Society of Cardiology. Clinical guidelines on the
prevention of cardiovascular disease in Denmark (“Kliniske retningslinier for
forebyggelse af kardiovaskulær sygdom i Danmark”). Danish Society of Cardiology,
2004 (www.cardio.dk).
12
Institute for Rational Pharmacotherapy. Lipid-lowering medicinal products –
Recommendations and background notes (“Lipidsænkende lægemidler Rekommandationer og baggrundsnotater”). Institute for Rational Pharmacotherapy,
2005 (www.irf.dk).
7
received statin treatment. Almost 15 percent of statin-treated patients
received the more expensive statins (atorvastatin, rosuvastatin and
fluvastatin). The expenses for these three medicinal products accounted for
65 percent of the total expenses for statins.
There are patients in whom the use of expensive statins is rational. This
applies, for instance, to patients whose cholesterol levels could not be
reduced by the use of, e.g., simvastatin, pravastatin or lovastatin.
Part of the consumption of the more expensive statins appears not to be
rational, however. This is partly because 41 percent of the consumption of
atorvastatin is at the 10 mg strength, and it must be assumed that a
substantial number of patients could achieve the same lipid reduction by
using simvastatin 40 mg, and partly because 31 percent of the new
atorvastatin users in 2005 (1,779 of 5,725) did not receive immediately
prior simvastatin treatment. On the other hand, developments in recent
years would appear to indicate a reduction in the consumption of
atorvastatin.
The total consumption over the last five years of the four types of lipidlowering medicines; statins, fibrates, anion exchangers and nicotinic acid
derivatives, shows that the increase is solely attributable to statins, which is
a rational development.
As concerns ezetimibe, extracts from the Register of Medicinal Product
Statistics at the Danish Medicines Agency show that some 900 individuals
bought ezetimibe at least once in 2005. Of these, 80 percent bought a statin
product at least once in the same period, while 20 percent did not buy a
statin product in this period.
We assess that there is presumably a basis for converting part of the
consumption to the more inexpensive statins that are eligible for general
reimbursement and continuing to encourage initial treatment with those
statins.
The Danish Medicines Agency will carefully monitor the consumption of
lipid-lowering medicines, including the distribution between the medicinal
products eligible for general reimbursement without restriction and the
medicinal products subject to restricted reimbursement.
Legal framework
The following are quotes from the provisions referred to in the above
decisions.
Section 144 (1) of the Danish Health Care Act states the following:
8
”Reimbursement is granted for purchases of prescription-only
medicinal products that have been granted general
reimbursement by the Danish Medicines Agency.”
Section 1 (1), (2) and (4) of the Executive Order on Reimbursement states
the following:
”Section 1. In pursuance of Section 7 (1)-(5) of the Danish
National Health Security Act, the Danish Medicines Agency
decides whether the national health security shall grant
general, including restricted, reimbursement for the purchase of
a medicinal product.
(2). When assessing whether a general reimbursement shall be
granted for a medicinal product, the Danish Medicines Agency
emphasises
1) whether the medicinal product has a safe and valuable
therapeutic effect on a well-defined indication, and
2) whether the relationship between the price of the medicinal
product and its treatment value is reasonable, see (3) and (4),
however.”
(4). Pursuant to the criteria established in (2) and (3) above, The
Danish Medicines Agency may decide that the national Health
Security reimbursement be conditional on the medicinal product
being prescribed with a view to treating specific diseases
(restricted reimbursement)…”
Presentation of the case
Decision to initiate reassessment
The Danish Medicines Agency initiated the reassessment of the
reimbursement status of lipid-lowering medicines (ATC Group C10) in
March 2006.
At its meetings on 22 March, 25 April, 13 June and 22 August 2006, the
Reimbursement Committee discussed the reimbursement status of lipidlowering medicines at the request of the Danish Medicines Agency.
The Reimbursement Committee’s recommendation on the reimbursement
status was ready on 7 September 2006.
On this background, the Danish Medicines Agency decided to initiate
procedures concerning changes of the reimbursement status for the lipidlowering medicines that were comprised by the reassessment, i.e.
authorised as at 7 August 2006, including your company’s authorised lipidlowering medicines.
9
Consultation
In a letter dated 29 September 2006, we asked you to submit any comments
to the recommendation of the Reimbursement Committee before 20
December 2006.
Concurrently, the following other stakeholders were consulted about the
Committee’s recommendation:
•
•
•
•
•
•
•
•
Other companies with authorised lipid-lowering medicines (ATC
Group C10)
Danish Society of Cardiology
Danish Medical Society
Danish College of General Practitioners
Danish Society of Internal Medicine
Danish Society for Clinical Pharmacology
Patient Forum
The Danish National Board of Health
We received responses from:
•
•
•
•
•
AstraZeneca A/S
Danish College of General Practitioners
Merck Sharp & Dohme
Pfizer ApS
The Danish National Board of Health
The consultation responses received were presented to the Reimbursement
Committee at its meeting on 16 January 2007. The Committee maintained
its recommendation of 7 September 2006 with the accompanying
justifications.
The consultation responses (in Danish only), the recommendation of the
Reimbursement Committee and the Danish Medicines Agency’s letter
about the consultation have been published at the Agency’s website
(www.dkma.dk – cf. “news”, notice of 15 February 2007).
The Danish Medicines Agency’s comments to the consultation responses
Two of the consultation responses voice concerns about the unilateral focus
on the price of the medicinal products in the reimbursement assessment.
It is an absolutely fundamental criterion in the assessment of the
reimbursement status of medicinal products that the price of the product
must be reasonable compared with its therapeutic value. The assessment as
to whether this criterion has been fulfilled thus requires careful
10
consideration of the therapeutic value of the medicinal product and
knowledge of its price.
Accordingly, the comments for the amendment of the Danish Health
Security Act by Act no. 1045 of 23 December 1998, which introduced the
current criteria for granting reimbursement, include the following
statement:
”In connection with authorising a medicinal product, it cannot
be required that a medicinal product fulfils a medical need, for
instance, and the price or other economic considerations do not
form part of the decision basis in relation to marketing
authorisation applications.
In contrast, the indication, use, price etc. of the medicinal
product form part of the basis for deciding whether a medicinal
product should be granted reimbursement or not. In addition to
the primary objective of granting public reimbursement for
treatment with medicines, the provisions of the Act in relation
to reimbursement consequently also aim at ensuring an
expedient use of health security funds and promote the rational
use of medicinal products. The fact that a medicinal product is
not subject to reimbursement should therefore not be
interpreted as an indication that it is less effective, less safe or
of a poorer quality than medicinal products subject to
reimbursement.”
The price of a medicinal product is thus an integral part of the Danish
Medicines Agency’s basis for deciding the reimbursement status.
The Committee’s recommendation to divide the lipid-lowering medicines
into two groups has also been questioned: medicinal products subject to
general reimbursement without restriction and medicinal products subject
to restricted reimbursement, including the fact that the medicinal products
within the individual groups are not comparable in every sense.
When the Danish Medicines Agency grants general reimbursement without
restriction for some medicinal products and restricted reimbursement for
others, this does not imply that the Danish Medicines Agency generally
assesses that medicinal products with the same reimbursement status are
comparable on all counts.
The Danish Medicines Agency assesses that the lipid-lowering medicinal
products comprised all fulfil the basic criterion that the therapeutic value of
the medicinal product is reasonable compared to the price. However, for
the medicinal products for which restricted reimbursement is granted, the
11
Danish Medicines Agency is of the opinion that the criterion has solely
been fulfilled in the cases stated in the restriction.
Internally within the group of medicinal products for which general
reimbursement without restriction is granted, as well as internally within
the group with restricted reimbursement, there will be differences in effect,
adverse reactions, the volume of documentation available, compliance in
the use of the products etc. These issues are not specific to lipid-lowering
medicines. What is decisive, however, is whether we assess in each specific
case that the medicinal product is overall eligible for reimbursement as
stated in the decision.
Finally, concerns have been raised about the fact that the proposed
reimbursement status limits the doctors’ possibilities of choosing the most
appropriate treatment.
In this context, it is noted that the Danish Medicines Agency shares the
opinion of the Reimbursement Committee that it will always be rational, as
a starting point, to initiate treatment with the cheaper statins eligible for
general reimbursement and then supplement or convert the treatment
regimen if necessary, e.g. if the treatment objective has not been reached or
the treatment is not tolerated.
The Danish Medicines Agency has noted that the Danish College of
General Practitioners, in their consultation response of 8 October 2006,
expressed their satisfaction with the changes recommended by the
Committee, as the College believes the changes to be evidence-based to the
greatest degree possible and to entail a considerable simplification of the
reimbursement rules.
Information
Doctors and pharmacies will receive information about the new
reimbursement status of lipid-lowering medicines in articles in medical
journals etc. Other stakeholders will receive a short notice referring to the
website of the Danish Medicines Agency where the decision and a brief
overview of the current and future reimbursement status will be published.
Conclusion
The division into general reimbursement and restricted reimbursement
requires the doctor – as always – to consider his or her prescription,
including the justification for prescribing lipid-lowering medicines subject
to restricted reimbursement and the choice between these medicines.
In principle, it will no longer be necessary to apply for single
reimbursement for the currently authorised lipid-lowering medicines.
12
However, it may still be an option in very special cases, e.g. for
cholestyramine intended for other uses than normal lipid-lowering therapy.
Complaints guidance
This decision may be brought before the Ministry of the Interior and
Health, Slotholmsgade 10-12, DK-1216 Copenhagen. This authority will
not, however, be able to assess the scientific evaluation made by the Danish
Medicines Agency.
Yours sincerely
Elisabeth Thomsen
Appendix:
A list of your products covered by the decision.
13